The phosphoproteome of choroid plexus epithelial cells following infection with Neisseria meningitidis

The Gram-negative bacterium Neisseria meningitidis, which causes meningitis in humans, has been demonstrated to manipulate or alter host signalling pathways during infection of the central nervous system (CNS). However, these complex signalling networks are not completely understood. We investigate the phosphoproteome of an in vitro model of the blood-cerebrospinal fluid barrier (BCSFB) based on human epithelial choroid plexus (CP) papilloma (HIBCPP) cells during infection with the N. meningitidis serogroup B strain MC58 in presence and absence of the bacterial capsule. Interestingly, our data demonstrates a stronger impact on the phosphoproteome of the cells by the capsule-deficient mutant of MC58. Using enrichment analyses, potential pathways, molecular processes, biological processes, cellular components and kinases were determined to be regulated as a consequence of N. meningitidis infection of the BCSFB. Our data highlight a variety of protein regulations that are altered during infection of CP epithelial cells with N. meningitidis, with the regulation of several pathways and molecular events only being detected after infection with the capsule-deficient mutant. Mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD038560

Digital single-operator pancreatoscopy for the treatment of symptomatic pancreatic duct stones: a prospective multicenter cohort trial

BACKGROUND  Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones. METHODS  Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs). RESULTS  40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively. CONCLUSION  DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients

Self-love and sociability: the ‘rudiments of commerce’ in the state of nature

Istvan Hont’s classic work on the theoretical links between the seventeenth-century natural jurists Hugo Grotius and Samuel Pufendorf and the eighteenth-century Scottish political economists remains a popular trope among intellectual and economic historians of various stamps. Despite this, a common criticism levelled at Hont remains his relative lack of engagement with the relationship between religion and economics in the early modern period. This paper challenges this aspect of Hont’s narrative by drawing attention to an alternative, albeit complementary, assessment of the natural jurisprudential heritage of eighteenth-century British political economy. Specifically, the article attempts to map on to Hont’s thesis the Christian Stoic interpretation of Grotius and Pufendorf which has gained greater currency in recent years. In doing so, the paper argues that Grotius and Pufendorf’s contributions to the ‘unsocial sociability’ debate do not necessarily lead directly to the Scottish school of political economists, as is commonly assumed. Instead, it contends that a reconsideration of Grotius and Pufendorf as neo-Stoic theorists, particularly via scrutiny of their respective adaptations of the traditional Stoic theory of oikeiosis, steers us towards the heart of the early English ‘clerical’ Enlightenment

International Delphi Consensus Study on disposable single-use endoscopy:A path to clinical adoption

Background/objective:Increasing infectious rate estimates and low microbiological surveillance affect safety of gastrointestinal endoscopy globally. Single use endoscopes and accessories have been claimed to improve safety, but there is lack of data on their indication and sustainability. We aimed to identify a series of best practice recommendations for the use of single use endoscopes and accessories using a modified Delphi. Methods/design: Consensus statements for the use of single use endoscopy and accessories were developed using a modified Delphi process, utilizing an international endoscopist expert panel of 62 experts from 33 nations. The main steps in the process were selecting the consensus group, conducting systematic literature reviews, developing statements, and anonymous voting on the statements until consensus was reached. High-risk patients were defined as those with multi-drug-resistant infections, immunosuppressive medication or chemotherapy, post-transplantation, or with severe neutropenia. Results:Of the 26 statements that were voted upon through two rounds, 17 statements reached consensus. Category 1: single use accessories (8 statements), related to defining recommendations for the use of single use accessories in all patient populations or high-risk patients. Category 2: clinical indication for single use endoscopes (9 statements), including indications to high-risk patients, protecting the endoscope apparatus and contamination measures in endoscopy units. Category 3: technical factors (4 statements), related to superior performance and technical specifications with the new innovation. Category 4: environmental issues (2 statements), concerning mechanisms that reduce the detrimental burden to the environment. Category 5: financial implications (3 statements), related to healthcare policies, cost neutrality and other financial associations of single use endoscopy. Conclusions: This is the first international initiative in determining clinical indications for single use endoscopy and accessories. The study's findings should serve as a framework for future physicians to guide future research and aid the proper evidence-based indications for the implementation of single use endoscopes in clinical practice.</p